Commercial Immunoglobulin Products Contain Neutralizing Antibodies Against Severe Acute Respiratory Syndrome Coronavirus 2 Spike Protein

Upasani, Vinit; Townsend, Katie; Wu, Mary; Carr, Edward J; Hobbs, Agnieszka; Dowgier, Giulia; Ragno, Martina; Herman, Lou S; Sharma, Satyawati; Shah, Devesh; Lee, Simon F K; Chauhan, Narendra Pal Singh; Glanville, Julie; Neave, Lucy; Hanson, Steven; Ravichandran, Sriram; Tynan, A; OʼSullivan, Mary J.; Moreira, Fernando; Workman, Sarita; Symes, Andrew; Burns, Siobhan O.; Tadros, Susan; Hart, Jennifer C L; Beale, Rupert; Gandhi, Sonia; Wall, Emma C; McCoy, Laura E; Lowe, David M.

doi:10.1093/cid/ciad368

Cited by 16 publications

(14 citation statements)

References 26 publications

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“…Our observations are consistent with those of previous trials of antibody-based therapies—administration of sufficient pathogen-specific antibodies via COVID-19 convalescent plasma leads to a reduced risk of disease progression, COVID-19-related hospitalization, and COVID-19-related death in immunocompromised patients in both outpatient and inpatient settings ( 5 , 19 ). Collectively, contemporary clinical data provide evidence to support the utility of high-titer convalescent plasma including vax-plasma as antibody replacement therapy in immunocompromised patients ( 17 , 20 , 21 ).…”

Section: Resultsmentioning

confidence: 93%

Outpatient treatment with concomitant vaccine-boosted convalescent plasma for patients with immunosuppression and COVID-19

Ripoll,

Tulledge-Scheitel,

Stephenson

et al. 2024

mBio

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Although severe coronavirus disease 2019 (COVID-19) and hospitalization associated with COVID-19 are generally preventable among healthy vaccine recipients, patients with immunosuppression have poor immunogenic responses to COVID-19 vaccines and remain at high risk of infection with SARS-CoV-2 and hospitalization. In addition, monoclonal antibody therapy is limited by the emergence of novel SARS-CoV-2 variants that have serially escaped neutralization. In this context, there is interest in understanding the clinical benefit associated with COVID-19 convalescent plasma collected from persons who have been both naturally infected with SARS-CoV-2 and vaccinated against SARS-CoV-2 (“vax-plasma”). Thus, we report the clinical outcome of 386 immunocompromised outpatients who were diagnosed with COVID-19 and who received contemporary COVID-19-specific therapeutics (standard-of-care group) and a subgroup who also received concomitant treatment with very high titer COVID-19 convalescent plasma (vax-plasma group) with a specific focus on hospitalization rates. The overall hospitalization rate was 2.2% (5 of 225 patients) in the vax-plasma group and 6.2% (10 of 161 patients) in the standard-of-care group, which corresponded to a relative risk reduction of 65% ( P = 0.046). Evidence of efficacy in nonvaccinated patients cannot be inferred from these data because 94% (361 of 386 patients) of patients were vaccinated. In vaccinated patients with immunosuppression and COVID-19, the addition of vax-plasma or very high titer COVID-19 convalescent plasma to COVID-19-specific therapies reduced the risk of disease progression leading to hospitalization. IMPORTANCE As SARS-CoV-2 evolves, new variants of concern (VOCs) have emerged that evade available anti-spike monoclonal antibodies, particularly among immunosuppressed patients. However, high-titer COVID-19 convalescent plasma continues to be effective against VOCs because of its broad-spectrum immunomodulatory properties. Thus, we report clinical outcomes of 386 immunocompromised outpatients who were treated with COVID-19-specific therapeutics and a subgroup also treated with vaccine-boosted convalescent plasma. We found that the administration of vaccine-boosted convalescent plasma was associated with a significantly decreased incidence of hospitalization among immunocompromised COVID-19 outpatients. Our data add to the contemporary data providing evidence to support the clinical utility of high-titer convalescent plasma as antibody replacement therapy in immunocompromised patients.

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Section: Resultsmentioning

confidence: 93%

Outpatient treatment with concomitant vaccine-boosted convalescent plasma for patients with immunosuppression and COVID-19

Ripoll,

Tulledge-Scheitel,

Stephenson

et al. 2024

mBio

View full text Add to dashboard Cite

show abstract

“…5,19 Collectively, contemporary clinical data provide evidence to support the utility of high-titer convalescent plasma including vax-plasma as antibody replacement therapy in immunocompromised patients. 17,20,21…”

Section: Resultsmentioning

confidence: 99%

Outpatient treatment with concomitant vaccine-boosted convalescent plasma for patients with immunosuppression and COVID-19

Ripoll,

Tulledge-Scheitel,

Stephenson

et al. 2023

Preprint

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Although severe coronavirus disease 19 (COVID-19) and hospitalization associated with COVID-19 are generally preventable among healthy vaccine recipients, patients with immunosuppression have poor immunogenic responses to COVID-19 vaccines and remain at high risk of infection with SARS-CoV-2 and hospitalization. Additionally, monoclonal antibody therapy is limited by the emergence of novel SARS-CoV-2 variants that have serially escaped neutralization. In this context, there is interest in understanding the clinical benefit associated with COVID-19 convalescent plasma collected from persons who have been both naturally infected with SARS-CoV-2 and vaccinated against SARS-CoV-2 (vax-plasma). Thus, we report the clinical outcome of 208 immunocompromised outpatients who were diagnosed with COVID-19 and who received contemporary COVID-19 specific therapeutics (standard of care group) and a subgroup who also received concomitant treatment with very high titer COVID-19 convalescent plasma (vax-plasma group) with a specific focus on hospitalization rates. The overall hospitalization rate was 1% (1 of 123 patients) in the vax-plasma group and 6% (5 of 85 patients) in the standard of care group, which corresponded to a relative risk reduction of 83%. Evidence of efficacy in nonvaccinated patients cannot be inferred from these data because 94% (196 of 208 patients) of patients were vaccinated. In vaccinated patients with immunosuppression and COVID-19, the addition of vax-plasma or very high titer COVID-19 convalescent plasma to COVID-19 specific therapies reduced the risk of disease progression leading to hospitalization.

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“…The antivirals Paxlovid (nirmatrelvir/ritonavir), remdesivir, and molnupiravir continue to be recommended, having significantly reduced hospitalisation and death with early variants and showing benefits in secondary endpoints such as time to recovery with the Omicrom variant [ 96 , 97 , 98 ]. With regards to supporting humoral immunity, studies of commercial immunoglobulin products have demonstrated substantial levels of anti-SARS-CoV-2 IgG present, sufficient to match values found in convalescent and vaccinated individuals once administered, with one study highlighting a large increase of the antibodies in patient sera post-administration in 35 individuals [ 99 , 100 , 101 ]. This latter study also demonstrated viral clearance following initiation of IgRT after a median of 20 days in antibody-deficient patients with pre-existing prolonged COVID-19 (median 189 days, maximum > 900 days) [ 100 ].…”

Section: Covid-19mentioning

confidence: 99%

“…With regards to supporting humoral immunity, studies of commercial immunoglobulin products have demonstrated substantial levels of anti-SARS-CoV-2 IgG present, sufficient to match values found in convalescent and vaccinated individuals once administered, with one study highlighting a large increase of the antibodies in patient sera post-administration in 35 individuals [ 99 , 100 , 101 ]. This latter study also demonstrated viral clearance following initiation of IgRT after a median of 20 days in antibody-deficient patients with pre-existing prolonged COVID-19 (median 189 days, maximum > 900 days) [ 100 ]. As one might expect due to widespread vaccination and post-infection immunity, the amount of anti-SARS-CoV-2 IgG present in immunoglobulin products appears to be increasing, suggesting increased protection for patients receiving the therapy moving forwards [ 102 ].…”

Section: Covid-19mentioning

confidence: 99%

The Scope and Impact of Viral Infections in Common Variable Immunodeficiency (CVID) and CVID-like Disorders: A Literature Review

Al-Hakim,

Kacar,

Savic

2024

JCM

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Common Variable Immunodeficiency (CVID) is a heterogeneous primary immunodeficiency disorder characterised by impaired antibody production, leading to recurrent infections and an increased susceptibility to viral pathogens. This literature review aims to provide a comprehensive overview of CVID’s relationship with viral infections, encompassing disease pathogenesis, key presenting features, specific monogenic susceptibilities, the impact of COVID-19, and existing treatment options. The pathogenesis of CVID involves complex immunological dysregulation, including defects in B cell development, antibody class switching, and plasma cell differentiation. These abnormalities contribute to an impaired humoral immune response against viral agents, predisposing individuals with CVID to a broad range of viral infections. Genetic factors play a prominent role in CVID, and monogenic drivers of CVID-like disease are increasingly identified through advanced genomic studies. Some monogenic causes of the CVID-like phenotype appear to cause specific viral susceptibilities, and these are explored in the review. The emergence of the COVID-19 pandemic highlighted CVID patients’ heightened predisposition to severe outcomes with viral infections. This review explores the clinical manifestations, outcomes, and potential therapeutic approaches for COVID-19 in CVID patients. It assesses the efficacy of prophylactic measures for COVID-19, including vaccination and immunoglobulin replacement therapy, as well as trialled therapies.

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Commercial Immunoglobulin Products Contain Neutralizing Antibodies Against Severe Acute Respiratory Syndrome Coronavirus 2 Spike Protein

Cited by 16 publications

References 26 publications

Outpatient treatment with concomitant vaccine-boosted convalescent plasma for patients with immunosuppression and COVID-19

Outpatient treatment with concomitant vaccine-boosted convalescent plasma for patients with immunosuppression and COVID-19

Outpatient treatment with concomitant vaccine-boosted convalescent plasma for patients with immunosuppression and COVID-19

The Scope and Impact of Viral Infections in Common Variable Immunodeficiency (CVID) and CVID-like Disorders: A Literature Review

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